title: Relationship between the cAMP levels in leukocytes and the cytokine balance in patients surviving gram negative bacterial pneumonia.
abstract: Lipopolysaccharide-stimulated leukocytes secrete proinflammatory cytokines including tumor necrosis factor-α and interleukin-12. Over-activation of host defense systems may result in severe tissue damage and requires regulation. Granulocyte colony-stimulating factor and interleukin-10 are candidate cytokines for inducing tolerance to lipopolysaccharide re-stimulation. We compared cytokines secreted by lipopolysaccharide-stimulated blood cells from patients who had survived gram negative bacterial pneumonia (Pseudomonas aeruginosa, Escherichia coli or Proteus mirabilis, n = 26) and age-matched healthy volunteers (n = 18). Interleukin-12p70 and tumor necrosis factor-α expression was significantly lower in patients (p = 0.0039 and p<0.001) compared to healthy controls, while granulocyte colony-stimulating factor production was markedly higher in patients (p<0.001). Levels of interleukin-10 were comparable. Granulocyte colony-stimulating factor expression was inversely correlated with interleukin-12p70 (R = -0.71, p<0.001) and tumor necrosis factor-α (R = -0.64, p<0.001) expression; interleukin-10 showed no significant correlation. In unstimulated leukocytes from patients, cAMP levels were significantly raised (p = 0.020) and were correlated inversely with interleukin-12p70 levels (R = -0.81, p<0.001) and directly with granulocyte colony-stimulating factor (R = 0.72, p = 0.0020), matrix metalloproteinase-9 (R = 0.67, p = 0.0067) and interleukin-10 (R = 0.54, p = 0.039) levels. Our results demonstrate that granulocyte colony-stimulating factor production by lipopolysaccharide-stimulated leukocytes is a useful indicator of tolerance induction in surviving pneumonia patients and that measuring cAMP in freshly isolated leukocytes may also be clinically significant.
authors.affiliation: Department of Surgery, Division of Frontier Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, Hiroshima 734-8551, Japan.
authors.forename: Tomio
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Keisuke
authors.initials: K
authors.lastname: Hayamizu
authors.forename: Seiji
authors.initials: S
authors.lastname: Marubayashi
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Shimizu
authors.forename: Aki
authors.initials: A
authors.lastname: Hamamoto
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Yamaguchi
authors.forename: Junji
authors.initials: J
authors.lastname: Hashizume
authors.forename: Takashi
authors.initials: T
authors.lastname: Onabe
authors.forename: Toshimasa
authors.initials: T
authors.lastname: Asahara
authors.forename: Hideki
authors.initials: H
authors.lastname: Ohdan